Abstract Alcohol use disorder (AUD) is a highly prevalent chronically relapsing disorder characterized by compulsion to seek and take alcohol and deficits in cognitive and executive function. These symptoms include disturbances in impulse-control, cognitive deficits, and inability to control alcohol intake. These behaviors are mediated through chronic alcohol-induced neuroadaptations in fronto-cortical regions of the brain, such as the anterior cingulate cortex (ACC) ? brain areas key for the ?top-down? inhibitory control over behavior. The ACC is also a hub for neuropathic pain, therefore, a potential key site for alcohol-induced hyperalgesia. Several gaps exist in our current knowledge of how these fronto-cortico regions of the brain mediate these executive function deficits as well as alcohol-induced hyperalgesia. One potential mechanism is through the sigma-1 receptor (Sig-1R). We have found that exposure to chronic intermittent ethanol (CIE) increases Sig-1R levels in the ACC. Sig-1R antagonists decrease excessive alcohol drinking and motivation in rats exposed to chronic intermittent ethanol (CIE), and they have been shown to alleviate neuropathic pain. Whether Sig-1Rs in the ACC play a role in excessive alcohol drinking, loss of inhibitory control, and allodynic state remains unclear. Here we hypothesize that hyperactivation of Sig-1R in the ACC is caused by chronic alcohol exposure and plays a key role in alcohol addiction and in the associated cognitive dysfunctions and allodynia. Sig-1R is a molecular chaperone that plays a key role in glutamatergic signaling, specifically through modulation of the N-methyl-D- Aspartate (NMDA) receptor. The NMDA receptor, especially within the ACC, plays a key role in pain sensitivity, alcohol intake and executive function. Thus, I hypothesize that the increases of Sig-1R levels leads to NMDA receptor redistribution in the ACC, increasing synaptic levels of NMDA subunit GluN2b, hereby driving the addiction process forward. To test these hypotheses, we will use a viral vector to knockdown Sig-1R in the ACC prior to exposing them to CIE. Rats will then be tested for excessive alcohol drinking, impulsive action, and mechanical allodynia. Furthermore, we will investigate physical interactions between Sig-1R and GluN2b and the effect of Sig-1R knockdown on subcellular localization of GluN2b. The results of these experiments will give important insights into the role of Sig-1Rs of the ACC in alcohol addiction, and may lead to the development of novel pharmacological treatments for AUD.